Addition of Paclitaxel to Primary Systemic Therapy Doubles the Chance of Avoiding Mastectomy

July 1, 2002

The addition of paclitaxel before surgery to primary systemic therapy with doxorubicin, followed by CMF

The addition of paclitaxel before surgeryto primary systemic therapy with doxorubicin, followed by CMF (cyclophosphamide[Cytoxan, Neosar], methotrexate, fluorouracil) has significant antitumoreffects, according to the preliminary results of the European Cooperative Trialin Operable Breast Cancer (ECTO) study. In the neoadjuvant arm, 52% of patientswith tumors larger than 2 cm had a complete clinical response and an additional29% had a partial response. The high antitumor activity led to a reduction inthe need for mastectomy and allowed for the performance of more conservativebreast surgery (68%) than in the adjuvant treatment group (34%).

Dramatic Downstaging

A clear benefit in terms of pathologic complete response wasseen in 22% of patients and associated with negative axillary nodes in 89% ofthese patients. Dr. Luca Gianni, director, division of Medical Oncology A,Istituto Nazionale Tumori, Milan, Italy, and chairman of the ECTO study said,"The extent of downstaging with primary systemic therapy with doxorubicinand paclitaxel followed by CMF was dramatic. Treatment was effective both at theprimary tumor and the axillary metastases, and this led to a significantincrease in the frequency of conservative surgery compared with conventionaltreatment."

For the study, patients with operable breast cancer (tumor >2 cm) were randomized to one of the following treatment strategies: (1) adjuvanttherapy with sequential doxorubicin followed by CMF, (2) adjuvant therapy withsequential doxorubicin and paclitaxel followed by CMF, or (3) primary systemictherapy (doxorubicin and paclitaxel followed by CMF). The trial investigatedwhether sequential chemotherapy for eight cycles prior to surgery would providea benefit compared with the usual approach of administering adjuvant therapyafter surgery and whether the addition of paclitaxel would provide furtherbenefits compared to non-paclitaxel-based chemotherapy.

Tolerable Side-Effect Profile

Treatment with paclitaxel in combination with doxorubicin andfollowed by CMF was well tolerated. The incidence of side effects was similar tothat seen in patients treated with conventional therapy. Treatment rarely causedfebrile neutropenia or grade 3 neurotoxicity, and there was no evidence of anyrelevant increase in cardiotoxicity with the addition of paclitaxel todoxorubicin, either as primary systemic therapy or adjuvant therapy.

"Primary systemic therapy provided a very good way oftesting directly the sensitivity of individual tumors to specific therapies andwill improve our ability to tailor treatments to specific needs of thepatient," Dr. Gianni concluded. "The preliminary results of this studyshow that the combination of paclitaxel and doxorubicin followed by CMF asneoadjuvant therapy has significant beneficial effects on locoregional tumorcontrol. As of today, we can only say that this translates as significantimprovement in the frequency of conservative breast surgery."

He added, "Paclitaxel is currently used to treat metastaticbreast cancer, but this study suggests that earlier use of paclitaxel in breastcancer can confer benefits seen so far in the ECTO study. These preliminaryresults are encouraging. In another 2 to 3 years time, survival data will tellus whether the addition of paclitaxel also provides long-term benefit."